Open Access
Cost-effectiveness of insulin pumps
To cite: Pollard DJ, Brennan A,
Dixon S, et al. Cost-
effectiveness of insulin pumps
compared with multiple daily
injections both provided with
structured education for
adults with type 1 diabetes:
a health economic analysis
of the Relative Effectiveness
of Pumps over Structured
Education (REPOSE) randomised
controlled trial. BMJ Open
2018;8:e016766. doi:10.1136/
bmjopen-2017-016766
►► Prepublication history and
additional material for this
paper are available online. To
view these files, please visit
the journal online (http://​dx.​doi.​
org/​10.​1136/​bmjopen-​2017-​
016766).
Received 8 March 2017
Revised 5 December 2017
Accepted 8 January 2018
For numbered affiliations see
end of article.
Correspondence to
Daniel John Pollard;
​d.​j.​pollard@​sheffield.​ac.​uk
compared with multiple daily injections
both provided with structured education
for adults with type 1 diabetes: a health
economic analysis of the Relative
Effectiveness of Pumps over Structured
Education (REPOSE) randomised
controlled trial
Daniel John Pollard,1 Alan Brennan,1 Simon Dixon,1 Norman Waugh,2
Jackie Elliott,3 Simon Heller,3 Ellen Lee,4 Michael Campbell,1 Hasan Basarir,5
David White,4 On behalf of the REPOSE group
Abstract
Objectives  To assess the long-term cost-effectiveness
of insulin pumps and Dose Adjustment for Normal Eating
(pumps+DAFNE) compared with multiple daily insulin
injections and DAFNE (MDI+DAFNE) for adults with type 1
diabetes mellitus (T1DM) in the UK.
Methods  We undertook a cost–utility analysis using the
Sheffield Type 1 Diabetes Policy Model and data from the
Relative Effectiveness of Pumps over Structured Education
(REPOSE) trial to estimate the lifetime incidence of diabetic
complications, intervention-based resource use and
associated effects on costs and quality-adjusted life years
(QALYs). All economic analyses took a National Health Service
and personal social services perspective and discounted
costs and QALYs at 3.5% per annum. A probabilistic
sensitivity analysis was performed on the base case. Further
uncertainties in the cost of pumps and the evidence used to
inform the model were explored using scenario analyses.
Setting  Eight diabetes centres in England and Scotland.
Participants  Adults with T1DM who were eligible to
receive a structured education course and did not have a
strong clinical indication or a preference for a pump.
Intervention Pumps+DAFNE.
Comparator MDI+DAFNE.
Main outcome measures  Incremental costs, incremental
QALYs gained and incremental cost-effectiveness ratios
(ICERs).
Results  Compared with MDI+DAFNE, pumps+DAFNE
was associated with an incremental discounted lifetime
cost of +£18 853 (95% CI £6175 to £31 645) and a gain
in discounted lifetime QALYs of +0.13 (95% CI −0.70
to +0.96). The base case mean ICER was £142 195 per
QALY gained. The probability of pump+DAFNE being cost-
effective using a cost-effectiveness threshold of £20 000
per QALY gained was 14.0%. All scenario and subgroup
Pollard DJ, et al. BMJ Open 2018;8:e016766. doi:10.1136/bmjopen-2017-016766
Research
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Strengths and limitations of this study
►► This study is the first cost-effectiveness analysis to
consider the use of insulin pumps for adults with
type 1 diabetes who are eligible to receive struc-
tured education course but not an insulin pump us-
ing current UK guidance.
►► The Relative Effectiveness of Pumps over Structured
Education (REPOSE) trial was the first trial to address
the question of whether insulin pumps were a clin-
ically effective treatment option in this population.
►► An existing validated model of type 1 diabetes and its
complications, developed during a previous National
Institute for Health Research funded programme
grant, was adapted and updated with evidence from
the REPOSE trial and more recent evidence on clini-
cal effectiveness, utilities and costs.
►► We considered a UK healthcare perspective to esti-
mate the key drivers of decision uncertainty.
►► The main limitations of the study are that the only
available evidence in long-term trends in HbA1c (the
key clinical outcome) was from several observation-
al studies, the analysis of diabetic ketoacidosis was
based on self-reported information rather than data
from inpatient admissions and that the trial only in-
cluded one type of insulin pump.
analyses examined indicated that the ICER was unlikely to
fall below £30 000 per QALY gained.
Conclusions  Our analysis of the REPOSE data suggests
that routine use of pumps in adults without an immediate
clinical need for a pump, as identified by National Institute
for Health and Care Excellence, would not be cost-
effective.
Trial registration number ISRCTN61215213.
1
Open Access
Introduction   observational study of pumps and MDI suggested that
People with type 1 diabetes mellitus (T1DM) are unable
to produce insulin due to autoimmune destruction of
their insulin-secreting beta cells. Those affected have to
inject insulin to prevent diabetic ketoacidosis (DKA) in
the short term, and in the long term, to prevent micro-
vascular and macrovascular disease. Insulin is generally
administered by intermittent subcutaneous injection with
the dose adjusted according to eating, physical activity and
current blood glucose levels. Therapy is designed to keep
blood glucose as close to normal as possible, to prevent
both microvascular complications and to reduce the risk
of macrovascular disease.1 A further aim of treatment is
to achieve as good a quality of life as possible, particularly
since self-management of the condition is challenging and
arduous, demanding the implementation of complex skills.
Historically, insulin was given twice a day, often as
premixed insulin, but such an approach imposes a
rigid lifestyle on people with T1DM and makes it diffi-
cult to maintain blood glucose levels close to normal.
Most individuals require intensive insulin therapy to
maintain tight glycaemic control. This approach and
its integration within a flexible lifestyle is promoted in
structured training courses, such as the Dose Adjust-
ment For Normal Eating (DAFNE)2 course and others.3
The principles of this multiple daily injections (MDI)
via subcutaneous injection approach involves the use
of quick-acting insulin injected before eating (with the
dose calculated according to the amount of carbohydrate
eaten) combined with long-acting background ‘basal’
insulin, usually given twice daily, to control blood glucose
in between meals.
As an alternative to MDI, insulin can be administered
by an insulin pump system in which insulin is delivered
throughout the day using a small, portable pump, connected
by a flexible plastic tube to a subcutaneous cannula. This
technology is relatively expensive compared with MDI.
Current National Institute for Health and Care Excellence
(NICE) guidelines recommend that all adults with T1DM
in the UK receive a structured education course of proven
benefit at a clinically appropriate time.4 Insulin pumps are
a treatment option for adults with T1DM who either have a
HbA1c above 69 mmol/mol (8.5%) or experience disabling
hypoglycaemia.5 Insulin pumps do not replace the need for
education, and it is currently recommended that specialist
teams should provide structured education programmes
and advice on diet, lifestyle and exercise for people using
an insulin pump.5
Use of pumps in T1DM varies substantially between
countries. In England, 11.7% of people with T1DM are
estimated to use a pump, which compares to around 40%
in the USA.6 7 It has been proposed that insulin pumps are
underused in the UK and that the glycaemic control of
adults with T1DM could be improved if pumps were used
more widely.8 Two NICE appraisals found that there was
insufficient evidence on insulin pump therapy compared
with MDI in which adults with T1DM used both long-
acting and short-acting insulins.9 10 Furthermore, a recent
2 Pollard DJ, et al. BMJ Open 2018;8:e016766. doi:10.1136/bmjopen-2017-016766
BMJ Open: first published as 10.1136/bmjopen-2017-016766 on 7 April 2018. Downloaded from http://bmjopen.bmj.com/ on 28 August 2018 by guest. Protected by copyright.
much of the previous benefit attributed to pumps may be
due to the additional education that pumps users require
when initiating therapy.11 Therefore, uncertainty remains
as to the clinical benefit and cost-effectiveness of pumps
as a treatment option for adults with T1DM.
The Relative Effectiveness of Pumps over Structured
Education (REPOSE) trial was conducted to assess if pumps
offered any additional benefit compared with MDI for the
treatment of adults with T1DM in the UK who are eligible
to attend a structured education course but do not have an
immediate clinical need for a pump. Participants in both
trial arms received a DAFNE course, which taught MDI
users to use long-acting and short-acting insulins appropri-
ately. In this paper, we present the cost-effectiveness analysis
of pumps+DAFNE compared with MDI+DAFNE for adults
in the UK with T1DM who are eligible to receive a struc-
tured education course but did not have a clinical need for
the immediate commencement of pump therapy.
Methods
Economic evaluation methods
The health economic analysis followed the prespecified
health economic analysis plan, which was outlined in the
trial protocol paper.12 Two approaches were undertaken
to assess the cost-effectiveness of pumps: an economic
evaluation alongside the clinical trial (EEACT) and a long-
term economic model to assess the lifetime outcomes.
In the EEACT, data on the costs and quality-adjusted
life years (QALYs) were obtained from data collected
in the REPOSE trial, whereas the long-term model esti-
mated the lifetime costs and QALYs based mainly on
the biomedical outcomes collected in the REPOSE trial.
All modelling analyses took a lifetime time horizon,
and all EEACT analyses took a 2-year (trial duration)
time horizon. The prespecified primary analysis relates
to the lifetime modelling, and as such, are reported in
this paper. The methods and results of the EEACT are
reported in online supplementary material A. In line with
NICE guidance, all economic analyses took a National
Health Service and personal social services perspective,
and costs and QALY outcomes were discounted at 3.5%.13
The economic model
The Sheffield Type 1 Diabetes Policy Model version 1.3.2,
henceforth ‘the model’, is an individual level simulation
model used to estimate the lifetime costs and QALYs asso-
ciated with pump+DAFNE and MDI+DAFNE. The most
recently published version of the model14 was updated
using data collected in the REPOSE trial at 12-month
and 24-month follow-up. Specifically, the level of HbA1c,
risk of severe hypoglycaemia, risk of DKA and the prob-
ability that an individual would switch insulin delivery
mechanism and costs related to the intervention (insulin
and MDI consumables, diabetes related contacts with
healthcare professionals, insulin pumps and the asso-
ciated consumables) were updated. Relevant literature

also informed the changes in HbA1c beyond the 2-year
trial duration and the probability of death from end-stage
renal disease (see online supplementary material B, page
2) in both arms. The model examines disease progression
over a lifetime using an annual time cycle. An individual’s
HbA1c determines their risk of progression for all diabetic
complications in the model, which include: nephropathy,
neuropathy, retinopathy, macular oedema, myocardial
infarction, stroke, heart failure, angina and severe hypo-
glycaemia and DKA. A higher HbA1c increases the risk of
progression for all complications in the model. Individuals
in the model are at risk of death from the incidence of:
nephropathy, myocardial infarction, stroke, heart failure,
angina and all-cause mortality. HbA1c indirectly effects
mortality in the model, as the probability death does not
differ by HbA1c; however, the risk of experiencing these
events is higher for someone with a higher HbA1c. The
model attaches utilities to health states and costs to
events, allowing the calculation of costs and QALYs over
a lifetime. Full details of how the model calculates the
incidence of diabetes complications is provided in Heller
et al (p. 104–106) and Thokala et al.14 15 The incremental
cost-effectiveness ratio (ICER) calculated was compared
with the £20 000 to £30 000 per QALY gained threshold
used by NICE.13 In each model run, the life course of
5000 individuals was simulated. This number of simu-
lated individuals was considered to be sufficiently robust
for decision making (see online supplementary material
B, page 1). All model analyses were conducted using
SIMUL8 professional 2010.16
The clinical data
The details of the methods used in the REPOSE trial have
been reported elsewhere.12 The eligibility criteria of the trial
included adults with T1DM if they were eligible to receive a
structured education course, did not have a clinical indica-
tion to receive a pump immediately, as determined by the
investigator, or did not have a strong preference to receive a
pump.12 The REPOSE trial was conducted in eight centres
in England and Scotland, involving 267 individuals. Out
of these 267 individuals, 260 had HbA1c data for at least
one postbaseline follow-up visit (intention to treat (ITT)
population) and 236 adhered to their randomised treat-
ment (per protocol population). Self-reported participant
information, which includes the number of DKA events,
EuroQol EQ-5D-3L, 12 item short form survey (SF-12) and
resource use were collected at baseline, 6 months, 1 year
and 2 years after attending DAFNE training. HbA1c, the
primary endpoint, was measured at baseline and at these
follow-up appointments. All inpatient admissions, the inci-
dence of severe hypoglycaemia and whether an individual
switched insulin delivery method were collected on an
ongoing basis. Information was collected on the staff time
spent delivering precourse fitting sessions for individuals
allocated to receive a pump. The cost of insulin pumps and
associated consumables in routine practice, and the insulin
pump consumables used by the REPOSE participants, were
collected from seven of the eight trial centres.
Pollard DJ, et al. BMJ Open 2018;8:e016766. doi:10.1136/bmjopen-2017-016766
Open Access
The simulation cohort
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To obtain the simulation cohort, participants’ REPOSE
data (n=260) were sampled with replacement 5000
times.17 This created a simulation cohort of 5000 individ-
uals for whom some would have missing baseline charac-
teristics. Each individual from REPOSE was included in
the simulation cohort a median of 19 times (IQR 16–22).
To obtain data values for these missing variables in the
simulation cohort, two imputation procedures were used.
A truncated regression procedure for missing continuous
variables (baseline: total cholesterol, high-density lipo-
protein (HDL) cholesterol, systolic blood pressure and
cost of insulin used in the year prior to baseline), in which
variables were limited to positive values, and a Poisson
procedure for missing categorical variables (gender). In
the truncated regression imputation procedure, all char-
acteristics with complete data in the REPOSE trial popu-
lation were used as predictive covariates. In the Poisson
imputation procedure, all characteristics with complete
data in the REPOSE trial population and the imputed
data for the continuous variables were used as predictive
covariates. In both imputation procedures, a single impu-
tation was used. As this was preformed in the simulation
cohort rather than the REPOSE data, the replications of
the individuals in the simulation cohort had different
data values if they had missing baseline data from the
trial. Identical individuals were simulated in both model
arms. A summary of the baseline characteristics and
completeness of data for the 260 REPOSE participants in
the ITT population and the 5000 individuals in the simu-
lation cohort are given in table 1.
The clinical effectiveness data
Statistical analyses of the REPOSE trial data were
conducted to estimate treatment switching, HbA1c, severe
hypoglycaemia and DKA. The main clinical results paper
is available; however, it differs in this paper as it focuses
on statistical in those people with a HbA1c greater than
or equal to 58 mmol/mol (7.5%).18 Information on long-
term changes in HbA1c was obtained from the available
literature and the REPOSE trial data. Unless otherwise
stated, all statistical analyses were conducted using STATA
V.13.1.19 Full details on the statistical methods used, the
results and how the analyses were incorporated into the
model are provided in online supplementary material B.
To estimate the incidence of treatment switching in
the first and second year of the model, a time-to-event
analysis was conducted using treatment switching as the
event of interest. Kaplan-Meier curves were plotted, and
parametric survival curves were fitted to the Kaplan-Meier
curves.20 21 Separate parametric survival models were
fitted to individuals randomised to pump+DAFNE and
MDI+DAFNE. The goodness of fit of the parametric
survival curves was assessed using the Akaike infor-
mation criterion, Bayesian information criterion and
visual assessment of the fit of the parametric curves to
the Kaplan-Meier curves at 1 and 2 years. As treatment
switching was included in the model, it is important to
3
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Table 1  The baseline characteristics of REPOSE participants and the simulated cohort
Characteristic REPOSE trial population (n=260) Simulated cohort (n=5000)
Continuous variables mean (SD) (% of individuals with data prior to imputation)
 Baseline HbA1c (mmol/mol) 76.0 (18.6) (100) 75.9 (18.2) (100)
 Baseline HbA1c (%) 9.1 (1.7) (100) 9.1 (1.7) (100)
 Age (years) 40.4 (13.4) (100) 40.4 (13.3) (100)
 Diabetes duration (years) 18.0 (12.5) (100) 18.0 (12.3) (100)
 Triglycerides (mmol/mol) 1.4 (1.0) (100) 1.4 (0.9) (100)
 Total cholesterol (mmol/mol) 4.9 (0.9) (99.6) 4.9 (0.9) (99.7)
 HDL cholesterol (mmol/mol) 1.6 (0.4) (96.5) 1.6 (0.4) (96.4)
 LDL cholesterol (mmol/mol) 2.8 (0.9) (96.2) 2.7 (0.9) (96.1)
 Systolic blood pressure 131.4 (16.4) (98.8) 131.3 (16.0) (98.9)
 Baseline cost of insulin £357.24 (147.65) (94.8) £360.39 (157.92) (98.4)
 Baseline cost of diabetes-related contacts £561.61 (885.92) (100) £571.63 (928.92) (100)
Categorical variables n/N (percentage) (% of individuals prior to imputation)
 Gender
   Female 104/260 (40.0) (40.0) 1990/5000 (39.8) (39.3)
   Male 152/260 (58.5) (58.5) 2950/5000 (59.0) (59.3)
   Missing 4/260 (1.5) (1.5) 0/5000 (0.0) (1.4)
 Physical activity
   Low 67/260 (25.8) (25.8) 1266/5000 (25.3) (25.3)
   Medium 128/260 (49.2) (49.2) 2471/5000 (49.4) (49.4)
   High 65/260 (25.0) (25.0) 1263/5000 (25.3) (25.3)
 Smoking status
   Current 50/260 (19.2) (19.2) 951/5000 (19.2) (19.2)
   Former 67/260 (25.8) (25.8) 1325/5000 (26.3) (26.3)
   Never 143/260 (55.0) (55.0) 2724/5000 (54.5) (54.5)
 Race
   White 258/260 (99.2) (99.2) 4959/5000 (99.2) (99.2)
   Black 2/260 (0.8) (0.8) 41/5000 (0.8) (0.8)
 Nephropathy
   No complications 239/260 (91.9) (91.9) 4600/5000 (92.0) (92.0)
   Microalbuminuria 13/260 (5.0) (5.0) 234/5000 (4.7) (4.7)
   Macroalbuminuria 7/260 (2.7) (2.7) 152/5000 (3.0) (3.0)
   Dialysis or transplant 1/260 (0.4) (0.4) 14/5000 (0.4) (0.4)
 Neuropathy
   No complications 238/260 (91.5) (91.5) 4599/5000 (92.0) (92.0)
   Neuropathy or ulcers 22/260 (8.5) (8.5) 401/5000 (8.0) (8.0)
 Retinopathy
   No complications 145/260 (55.8) (55.8) 28/5000 (56.0) (56.0)
   Background diabetic retinopathy 91/260 (35.0) (35.0) 1740/5000 (34.8) (34.8)
   Proliferative diabetic retinopathy 24/260 (9.2) (9.2) 465/5000 (9.3) (9.3)
 Myocardial infarction
   No complications 255/260 (98.1) (98.1) 4896/5000 (97.9) (97.9)
   Myocardial infarction 5/260 (1.9) (1.9) 104/5000 (2.1) (2.1)
 Stroke
   No complications 259/260 (99.6) (99.6) 4983/5000 (99.7) (99.7)
   Stroke 1/260 (0.4) (0.4) 17/5000 (0.3) (0.3)

Continued

4 Pollard DJ, et al. BMJ Open 2018;8:e016766. doi:10.1136/bmjopen-2017-016766


Table 1  Continued 
Characteristic REPOSE trial population (n=260)
 Heart failure
   No complications 259/260 (99.6) (99.6)
   Heart failure 1/260 (0.4) (0.4)
 Angina
   No complications 257/260 (98.9) (98.9)
   Angina 3/260 (1.2) (1.2)
HDL, high-density lipoprotein; LDL, low-density lipoprotein; REPOSE, Relative Effectiveness of Pumps over Structured Education.
adjust the modelled treatment effectiveness and cost of
treatment for those individuals who switch. If individuals
switched treatment, then their HbA1c was assumed to
change as though they had been allocated to the other
arm. No explicit effect of switching on the incidence rate
ratio (IRR) associated with the model arms for either
severe hypoglycaemia or DKA was included. However, due
to the change in HbA1c associated with switching, individ-
uals who switched from pump to MDI were at a lower risk
of severe hypoglycaemia and at a higher risk of DKA. The
opposite was true for those individuals who switched from
MDI to pump. In the base case analysis, the HbA1c effect
of pump+DAFNE compared with MDI+DAFNE was esti-
mated in the per protocol population, as the people who
switched treatment were excluded from this population.
To estimate each individual’s HbA1c in the model, a
beta regression was fitted to the HbA1c data collected
in REPOSE for all individuals in the per-protocol popu-
lation at the 1-year and 2-year follow-up.22 Bounds were
placed on the beta regression so that HbA1c was between
the clinically plausible bounds of 29 mmol/mol (4.8%)
and 201 mmol/mol (20.5%), which were provided by
two clinical experts in the REPOSE trial management
group. Missing data were observed for HbA1c values in
the per-protocol population at 6 months (2.1% missing),
1 year (4.2% missing) and 2 years (4.2% missing). Full
details on the imputation procedure used to account for
the missing data and the specification of the beta regres-
sion are provided in online supplementary material B
(see p. 8). The effects in a beta regression are not easily
interpretable by themselves; however, information can be
obtained on the direction of effect.
The expert opinion of clinical members involved in
the literature review of clinical studies for the REPOSE
trial was sought to identify studies with long-term data
on HbA1c for the type of pumps used in the trial and
people who used MDI after DAFNE. Three articles on the
long-term trends in HbA1c for pump users23–25 and two
articles on the long-term trends in HbA1c for MDI users
post-DAFNE26 27 were used to estimate yearly changes in
HbA1c for each model arm. The average annual increase
in HbA1c was calculated for each study by calculating
yearly increase in HbA1c between the lowest observed
HbA1c value and the last follow-up point in the study
where the sample size was greater than one quarter of the
Pollard DJ, et al. BMJ Open 2018;8:e016766. doi:10.1136/bmjopen-2017-016766
Open Access
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Simulated cohort (n=5000)
4934/5000 (99.6) (99.6)
18/5000 (0.4) (0.4)
4934/5000 (98.7) (98.7)
66/5000 (1.3) (1.3)
initial sample size. An SE could not be directly calculated,
as we did not have access to the patient level data from the
studies. Instead, data on the SD of the change in HbA1c
between the 1-year and 2-year follow-ups specific to each
REPOSE trial arm were used to inform the uncertainty in
this parameter. These SDs were divided by the square root
of the combined sample size of the studies used to inform
the mean effect to estimate SE for this parameter.
Negative binomial regressions were used to estimate the
risk of severe hypoglycaemia and DKA in the ITT popu-
lation of REPOSE using the Zellig package in R V.3.2.0.
Negative binomial regressions were fitted separately to
severe hypoglycaemia and DKA events and to the first and
second years of follow-up data. The regressions fitted to
the second year data were used to estimate the incidence
of severe hypoglycaemia and DKA in all model time
cycles, except for the first time cycle. This assumption was
based on clinical expert opinion, which was confirmed
by the trial management group, that the first 6 months of
using a pump was associated with a learning period, and
after this time, the incidence of severe hypoglycaemia
and DKA would decrease.
Costs and utilities
The costs and health state utility values used for each
health state in the model are provided in table 2 and
table 3, respectively. All costs were reported in 2013/2014
prices. Costs sourced from evidence in previous years
were inflated to 2013/2014 prices using the hospital
and community health services pay and prices index.28
The cost of insulin and MDI consumables used, cost of
diabetes related contacts with healthcare professionals
and cost of the pump intervention costs were estimated
separately for both year 1 and year 2 of the REPOSE
trial. The unit cost of insulin and MDI consumables used
was obtained from the British National Formulary and
Health & Social Care Information Centre, the unit cost
of diabetes related contacts were obtained from NHS
reference costs and unit cost of an insulin pump (with its
associated consumables) was obtained from a survey of
the REPOSE trial sites.29–31 Table 2 part A shows the six
regression formulae that estimate an individual’s annual
cost for each of these components as a function of: their
baseline HbA1c, which treatment they start the year on
(MDI or pump), whether they switch treatment and also
5
6
Table 2  The health state cost parameters used in the Sheffield Type 1 Diabetes Policy Model
Part A: seemingly unrelated regression functions for estimated costs in year 1 and ongoing based on REPOSE trial data (multivariate normal distributions*)
Annual cost of Annual cost of Annual cost of insulin Annual cost of insulin
insulin and MDI insulin and MDI pump and associated pump and associated
consumables consumables Annual cost of DRC Annual cost of DRC consumables consumables
(year 1) (ongoing) (year 1) (ongoing) (year 1) (ongoing) Sources
Open Access

Multiplier for the baseline DRC – – +0.11 +0.03 – – REPOSE trial data in year 1.
cost (<<<NO ENTITY>>>1) (year 1  costs).
REPOSE trial data in year 2.
(ongoing costs).
NHS reference costs.30
Pump costing survey.
Multiplier for the baseline +0.97 +1.04 – – – –
insulin cost (<<<NO
ENTITY>>>2)
Multiplier for the baseline +5.08 +12.81 −21.66 +12.15 – –
HbA1c (DCCT % scale) (<<<NO
ENTITY>>>3)
Receiving pump at the start of −517.91 −527.64 +129.08 +88.99 +2056.11 +2050.99
the year (<<<NO ENTITY>>>4)
Switch from pump to MDI +554.47 +153.35 +280.16 −47.10 −1143.68 −905.03
(<<<NO ENTITY>>>5)
Switch from MDI to pump 0† −353.27 +733.95 +201.93 +804.57 +1134.27
(<<<NO ENTITY>>>6)
Constant (<<<NO ENTITY>>>0) +381.77 +324.53 +415.46 +299.80 0.00 0.00

Part B: costs of DAFNE fixed parameters

Health state Mean cost (£) SE Source Health state Mean cost (£) SE Source
 Cost of a DAFNE course 363.10 None DAFNE Fact Sheet Cost of precourse fitting 28.82 None DAFNE Fact Sheet Six37 and
Six37 session for pump users REPOSE trial data
Part C: costs of adverse events, comorbidities and complications Gamma distributions
Health state Mean Cost (£) SE Source Health state Mean cost (£) SE Source

Adverse events
 Hypoglycaemia 187 18.69 Heller et al14 DKA with hospitalisation 1399 140 NHS reference costs38
Nephropathy
 Ongoing yearly cost of 36 3.56 BNF39 and McEwan Ongoing yearly cost of 36 3.56 BNF39 and McEwan et al40
microalbuminuria et al40 microalbuminuria ongoing
 Ongoing yearly cost of ESRD 24 436 2444 NHS reference Death due to ESRD 0 0 Assumed equal to zero
costs38
Neuropathy
 Clinically confirmed 271 27.14 Currie et al41 Clinical neuropathy 271 27.14 Currie et al41
neuropathy
 Diabetic foot syndrome 2848 285 NHS Reference PAD with amputation 7221 722 NHS Reference costs38
costs38 (year 1)
 Ongoing yearly cost of PAD 439 43.93 McEwan et al40
with amputation

Continued

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 Table 2  Continued 
Part C: costs of adverse events, comorbidities and complications Gamma distributions
Health state Mean Cost (£) SE Source Health state Mean cost (£) SE Source

Retinopathy
 Background retinopathy 145 14.47 McEwan et al40 Proliferative retinopathy 661 66.11 McEwan et al40
 Macular oedema (year 1) 5710 571.0 NICE,42 BNF43 Macular oedema (year 2) 3416 341.6 NICE,42 BNF43
42 43
 Macular oedema (year 3) 2562 256.2 NICE, BNF Macular oedema (ongoing) 277 27.7 NICE,42 BNF43
44
 Blindness (year 1) 1584 158 Clarke et al Blindness (ongoing) 519 51.88 Clarke et al44
Cardiovascular
 First MI (year 1) 6788 679 Clarke et al44 Second MI (year 1) 6788 679 Clarke et al44

Pollard DJ, et al. BMJ Open 2018;8:e016766. doi:10.1136/bmjopen-2017-016766

44
 Final MI (year 1) 6788 679 Clarke et al Ongoing yearly cost of 904 90.43 Clarke et al44
an MI
 Fatal MI 2101 210 Clarke et al44 Heart Failure (year 1) 3818 382 Clarke et al44
44
 Heart failure (ongoing) 1173 117 Clarke et al Fatal HF 3818 382 Clarke et al44
 First stroke (year 1) 4361 436 Clarke et al44 Second stroke 4361 436 Clarke et al44
44
 Fatal stroke 5684 568.45 Clarke et al First stroke (ongoing) 559 55.90 Clarke et al44
44
 Angina (year 1) 3397 340 Clarke et al Angina (ongoing) 951 95.09 Clarke et al44

*The variance covariance matrices used to parameterise the multivariate normal distribution are provided in online supplementary material B tables 4, 7 and 12.
†This variable was included in the original regressions; however, the model would converge when this covariate was included, so this parameters is taken to be a zero value in the total cost formula.
–This value was not included as a covariate in the regression formula and is taken to be a zero value in the total cost formula.
The cost for each total cost in part A is calculated using the following formula:
Total cost=β0+β1*individual’s baseline diabetes-related contact cost+β2*individual’s baseline insulin cost+β3*individual’s baseline HbA1c (DCCT % scale)+β4*individual’s treatment at the start of the year (1=pump,
0=MDI)+β5*(1=switched from pump to MDI, 0=did not switch from pump to MDI)+β6*(1=Switched from MDI to pump, 0=did not switch from MDI to pump).
BNF, British National Formulary; DAFNE, Dose Adjustment for Normal Eating; DCCT, Diabetes Control and Complications Trial; DKA, diabetic ketoacidosis; DRC, diabetes related contacts; ESRD, end-stage renal
disease; HF, heart failure; MDI, multiple daily injections; MI, myocardial infarction; NHS, National Health Service; NICE, National Institute for Health and Care Excellence; PAD, peripheral arterial disease; pump, insulin
pumps; REPOSE, Relative Effectiveness of Pumps over Structured Education.
Open Access

7
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Open Access

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Table 3  The base case utility parameters
Beta distribution
Health state for event Utility SE Alpha Beta Source
Baseline utility value
 Male with type 1 diabetes and no 0.866 0.010 947.79 146.90 Peasgood et al45
complications
Gamma distribution
Disutility SE Alpha Beta Source
Complications or covariates
 Female with type 1 diabetes and no 0.0236 0.008 8.70 0.003 Peasgood et al45*
complications
Adverse events‡
  Severe hypoglycaemia −0.002 −0.002 1 0.002 Peasgood et al45
 Diabetic ketoacidosis −0.0091 −0.01 0.83 0.01 Peasgood et al45*
Nephropathy§
 Microalbuminuria 0 Assumption
  Microalbuminuria −0.017 0.01 2.89 0.01 Coffey et al46
  ESRD −0.078 0.026 9 0.01 Coffey et al46
Neuropathy§ (applied to the history of events)
  Clinical neuropathy −0.055 0.01 30.25 0.002 Coffey et al46
  Clinically confirmed neuropathy −0.055 0.01 30.25 0.002 Coffey et al46
  Diabetic foot syndrome −0.1042 −0.119 0.77 0.14 Peasgood et al45
  PAD with amputation −0.1172 −0.055 4.54 0.03 Peasgood et al45*
Retinopathy§ (applied to the history of events)
  Background retinopathy −0.0544 −0.023 5.59 0.01 Peasgood et al45
  Proliferative retinopathy −0.0288 −0.026 1.23 0.02 Peasgood et al45
  Blindness −0.208 0.013 256 0.001 Coffey et al46
Cardiovascular§ (applied to the history of events)
  MI (first year) −0.065 0.03 4.69 0.01 Alva et al47
  MI (subsequent years) −0.057 0.03 3.61 0.02 Alva et al47
  Heart failure −0.101 0.032 9.96 0.010 Alva et al47
  Stroke −0.165 0.035 22.22 0.007 Alva et al47
  Angina −0.09 0.018 25 0.004 Clarke et al48†
*A parameter value was not available in the author’s preferred statistical model.
†Value is presented in table 5 as ischaemic heart disease.
‡These disutilites are applied transiently to the number of these events in each year.
§These disutilites are applied to the history of ever having had one of these events.
ESRD, end-stage renal disease; MI, myocardial infarction; PAD, peripheral arterial disease.

the participants’ self-reported use of insulin and level of
contact with healthcare professionals prior to recruitment
to the trial. Details on how these parameters were used to
estimate the costs in the model are provided in table 2.
Scenario and subgroup analyses
For the base case, a probabilistic sensitivity anal-
ysis (PSA) was conducted where each parameter was
sampled from its probability distribution, the results
were recorded, the process was repeated 500 times and
the averages from these 500 model runs were reported.
This number of PSA runs was considered to be suffi-
cient to allow for robust decision making based on the
model results (see online supplementary material B,
page 1). All statistical models, except for the risks of
severe hypoglycaemia and DKA, for which the outcomes
were directly simulated in R V.3.2.0, were included in
the model using a multivariate normal distribution.32
The long-term changes in HbA1c were assumed to be
distributed using independent normal distributions for
each model arm. Deterministic scenario analyses were
undertaken to assess the robustness of the results. The
key scenario analyses for the model include: uncertainty
in the estimates of treatment effectiveness, the timing
of HbA1c changes in the model, the utility decrement

8 Pollard DJ, et al. BMJ Open 2018;8:e016766. doi:10.1136/bmjopen-2017-016766


for blindness (−0.26)33 and the cost of insulin pumps
and insulin pump consumables.
A two-way deterministic threshold analysis was conducted
to assess the HbA1c reduction and/or annual cost reduc-
tion necessary to potentially make pumps cost-effective
in the UK. All threshold analysis runs were conducted
deterministically. In this analysis, each individual’s HbA1c
was estimated as though they received MDI. Then those
individuals in the pump arm received a fixed change in
HbA1c. This change in HbA1c was varied at 10 different
values between −3.3mmol/mol (−0.3%) and −13.1mmol/
mol (−1.2%), and annual cost of insulin pumps were also
varied between 100% of the observed cost in the REPOSE
trial and 50% of the observed cost.
Deterministic subgroup analyses were conducted in the
following populations:
1. baseline HbA1c <69 mmol/mol (8.5%)
2. baseline HbA1c ≥69 mmol/mol (8.5%)
3. baseline HbA1c ≥58 mmol/mol (7.5%)
4. 69 mmol/mol (8.5%) >baseline HbA1c ≥58 mmol/
mol (7.5%)
5. 80 mmol/mol (9.5%) >baseline HbA1c ≥69 mmol/
mol (8.5%)
6. baseline HbA1c ≥80 mmol/mol (9.5%)
7. all individuals in the per protocol population.
The subgroup analyses were conducted by resampling
the simulation cohort from the individuals who met each
of these criteria in the ITT population.
Figure 1  The trace of: (A) the mean HbA1c in each year of the model, (B) the mean HbA1c ignoring the effects of death and
treatment switching, (C) the number of people alive in each year of the model in both arms over 30 years. DCCT,   Diabetes
Control and Complications Trial; MDI, multiple daily injection.
Pollard DJ, et al. BMJ Open 2018;8:e016766. doi:10.1136/bmjopen-2017-016766
Open Access
Results
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Clinical effectiveness data
Treatment switching
The analysis of treatment switching in the REPOSE trial
suggested that an exponential curve provided the best fit
to the data for individuals receiving pump+DAFNE and a
Weibull curve provided the best fit for individuals in the
MDI+DAFNE arm.
HbA1c
The results of the analysis of HbA1c data suggested that
pump+DAFNE compared with MDI+DAFNE was associated
with statistically insignificant HbA1c reductions in both year
1 and in year 2. The analysis of the literature for long-term
trends in HbA1c suggested that weighted average annual
progression of HbA1c was +0.568 mmol/mol (+0.052%) per
annum in the pump+DAFNE arm and +0.590 mmol/mol
(+0.054%) per annum in the MDI+DAFNE arm. The esti-
mated standard errors for the long-term trends in HbA1c
were of 0.627 mmol/mol (0.040%) for MDI+DAFNE and
0.627 mmol/mol (0.057%) for pump+DAFNE.
These data produce a trace of HbA1c as in figure 1.
The solid lines show the average HbA1c in the model for
each year. The dotted lines show what the HbA1c would
have been in each year, if a higher HbA1c did not have
an indirect effect on the number of deaths in the model
or treatment switching effects. The dashed line shows the
number of people remaining alive in each year and is
9
Open Access
plotted on the secondary axis. As expected from the base
case clinical results, the MDI+DAFNE arm has a higher
HbA1c than the pumps+DAFNE  arm, and this effect
slightly increases over time
Severe hypoglycaemia and DKA
The results of the negative binomial models used to esti-
mate the incidence of DKA indicated that pump+DAFNE
compared with MDI+DAFNE was associated with more
DKA events in the first year (IRR 1.40, 95% CI 0.55 to
3.58) but fewer events in year 2 (IRR 0.93, 95% CI 0.23 to
3.69). The results of the negative binomial models used
to estimate the incidence of severe hypoglycaemia indi-
cated that pump+DAFNE compared with MDI+DAFNE
was associated with more severe hypoglycaemic events in
year 1 (IRR 1.33, 95% CI 0.49 to 3.65) but fewer events in
the second year (IRR 0.35, 95% CI 0.08 to 1.44).
Base case results
Table 4 shows the base case results for the long-term
cost-effectiveness analysis using the PSA. For the
pump+DAFNE arm, the mean costs of the intervention
are £42 124 discounted over the lifetime horizon, which
compares with £19 829 for the MDI+DAFNE arm. This
leads to an increase in intervention costs of £21 295 over a
person’s lifetime. The QALYs lived, prior to applying the
utility decrements associated with diabetic complications,
in the pump+DAFNE arm is 13.91 QALYs compared with
14.03 QALYs in the MDI+DAFNE arm, a difference of 0.11
QALYs. The differential incidence of adverse events in the
pump+DAFNE arm compared with the MDI+DAFNE arm
leads to a lower costs (−£371) and higher QALYs (+0.00)
per person. The reduced incidence of diabetic compli-
cations in the pump+DAFNE arm leads to lower costs
(−£2070) and more QALYs (+0.01) per person. The net
incremental lifetime cost of pump versus MDI is there-
fore estimated as £18 853 (95% CI £6175 to £31,645)
per person. The net incremental QALY gain per person
is 0.13 (95% CI −0.70 to +0.96) QALYs per person. The
ICER associated with pump+DAFNE was £142 195 per
QALY gained. This is considerable above the £30 000
per QALY threshold, which is the higher limit at which
NICE would usually consider interventions to be cost-ef-
fective.13  Figure 2A shows that this result is subject to a
small degree of uncertainty, as in 14.0% of the PSA runs,
pump+DAFNE would be considered as being cost-effec-
tive using the lower end of the range used by NICE.
Scenario and subgroup analyses
The results of 11 scenario analyses are presented
in figure 2B. None of the scenario analyses showed
pump+DAFNE to be cost-effective versus MDI+DAFNE.
The lowest ICER found (£31 747 per QALY gained) was
for scenario 3 in which yearly cost of pumps and consum-
ables was halved.
The results of the two-way price and effectiveness
threshold analysis are given in table 5. When the annual
pump cost is assumed to be 100% of the prices observed
10
in REPOSE, then the analysis shows that the reduction in
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HbA1c (for pump compared with MDI) would need to
be 12.0 mmol/mol (1.1%) or more, for pump to have an
ICER below £20 000 per QALY gained. When the annual
cost is 25% lower, then a HbA1c reduction of more than
7.7 mmol/mol (0.7%) would be needed to have an ICER
below £20 000 per QALY gained. When the annual cost is
halved, then a HbA1c reduction of 3.3 mmol/mol (0.3%)
would be sufficient to have an ICER below £20 000 per
QALY gained.
The result of the subgroup analyses are presented in
figure 2C. Similarly to the scenario analysis, no subgroup
was identified in which pump+DAFNE would be likely
to be considered more cost-effective than MDI+DAFNE.
The most cost-effective subgroup was those individuals
with a baseline HbA1c greater than or equal to 80 mmol/
mol (9.5%), with an ICER of £96 394 per QALY gained
versus MDI+DAFNE.
Discussion
This is the first study to examine the marginal benefits
and cost-effectiveness of insulin delivered using pumps
over MDI when both groups have had structured educa-
tion, in patients without an immediate clinical need for
an insulin pump, as recommended by NICE. Our find-
ings show that providing pumps for this wider group of
adults with T1DM would be unlikely to be considered
cost-effective in the UK because the estimated ICER was
just over £142 000, substantially higher than the £30 000
per QALY upper limit often used by UK decision makers.
This finding is also valid in all scenario and subgroup
analyses examined. The threshold analysis indicates that
if new insulin pump technology is developed and the
costs are similar to current insulin pumps, a trial would
have to demonstrate a HbA1c reduction in the region of
11 mmol/mol (1.0%) to 13 mmol/mol (1.2%) compared
with MDI+DAFNE for the new technology to be consid-
ered cost-effective in the UK for the population analysed
in this study. Conversely, if insulin pump prices were
halved, then reductions of only 3 mmol/mol compared
with MDI are required.
The key strengths of this study are that it is based on
a rigorously conducted cluster RCT with economic data
directly collected during the study. Data completeness
for the primary outcome was very high at 95%. The
study uses an individual level simulation model of type
1 diabetes disease progression over a lifetime horizon.
The study does have limitations in terms of the evidence
used to inform the long-term changes in HbA1c, which
were based on five observational studies with follow-up
ranging from 3.7 to 10 years, rather than trials with long
follow-up periods. Also, as REPOSE is the first study to
assess the effectiveness of pumps+DAFNE, the long-term
evidence was based on observational studies of pumps
in which the education component is likely to have
been different from the DAFNE structured education
provided in the REPOSE trial. Our PSA has incorporated
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Table 4  Long-term cost-effectiveness analysis: base case results using probabilistic sensitivity analysis
MDI+DAFNE Pump+DAFNE Incremental
Mean lifetime discounted costs per person
 Intervention costs
  Insulin and MDI consumables £12 215 £5476 −£6740
  Diabetes-related contacts £5023 £6289 £1266
  Insulin pumps and pump consumables £2228 £28 967 £26 739
  DAFNE course £363 £392 £29
 Subtotal intervention costs £19 829 £41 124 £21 295
 Adverse event costs
  Severe hypoglycaemia £133 £41 −£92
  Diabetic ketoacidosis £1161 £882 −£279
 Subtotal cost of adverse events £1294 £922 −£371
 Long-term complication costs
  Nephropathy £40 786 £38 853 −£1933
  Neuropathy £1859 £1805 −£53
  Retinopathy+macular oedema £6365 £6263 −£102
  Myocardial infarction £1838 £1844 £6
  Heart failure £607 £609 £2
  Stroke £253 £254 £0
  Angina £1134 £1143 £8
 Total cost of long-term complications £52 841 £50 771 −£2070
 Total costs £73 964 £92 817 £18 853
(95% CI £6175 to £31 645)
Mean undiscounted life years per person
  Total life years 28.3181 28.7999 0.3790
(95% CI −2.7392 to 3.3403)
Mean discounted QALYs per person
  QALYs lived 13.9145 14.0292 0.1147
  (excluding decrements due to complications)
  QALYs lost due to adverse events
  Severe hypoglycaemia −0.0014 −0.0004 0.0009
  Diabetic ketoacidosis −0.0075 −0.0057 0.0018
 Subtotal QALYs due to adverse events −0.0088 −0.0061 0.0027
 QALYs lost due to complications
  Nephropathy −0.1853 −0.1792 0.0061
  Neuropathy −0.3092 −0.3010 0.0082
  Retinopathy+macular oedema −0.3316 −0.3293 0.0022
  Myocardial infarction −0.0528 −0.0532 −0.0004
  Heart failure −0.0385 −0.0387 −0.0002
  Stroke −0.0343 −0.0345 −0.0002
  Angina −0.0754 −0.0761 −0.0007
 Subtotal QALYs lost due to complications −1.0271 −1.0120 0.0152
 Total QALYs 12.8785 13.0111 0.1326
(95% CI −0.7087 to 0.9623)
Summary
 Total mean discounted costs per person £80 471 £99 337 £18 853
(95% CI £6175 to £31 645)
Continued

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Open Access

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Table 4  Continued 
MDI+DAFNE Pump+DAFNE Incremental
 Total mean undiscounted life years per person 28.3181 28.7999 0.3790
(95% CI −2.7392 to 3.3403)
 Total mean discounted QALYs per person 12.8785 13.0111 0.1326
(95% CI −0.7087 to 0.9623)
 ICER (£/QALY gained) £142 195
 Probability that pump+DAFNE is cost-effective at 14.0%
a threshold of £20 000 per QALY gained

DAFNE, Dose Adjustment for Normal Eating; ICER, incremental cost-effectiveness ratio; MDI, multiple daily injections;
pump, insulin pumps; QALY, quality-adjusted life year.

uncertainty around these estimates. Second, the analysis
of rates of DKA was based on self-reported occurrence
of DKA in REPOSE (the same method as used in other
recent trials of DAFNE Heller et al, chapter 8),14 rather
than corroborated data on inpatient admissions that had
a smaller number of events and could not be analysed
statistically. Third, only one pump type was assessed in the
trial, and some caution may be needed when considering
extrapolating results to modern pumps with autosuspend
features. Fourth, the results of the threshold analysis used
to determine what the effectiveness of pumps would need
to be considered cost-effective should be interpreted with
some degree of caution for two reasons. First, we used
a fixed HbA1c effect for every individual, rather than
a method that accounts for heterogeneous treatment
responses, and second, we assume switchers from MDI to
pump get the fixed HbA1c reduction and switchers from
pump to MDI get the same fixed HbA1c increase. In an

Figure 2  The results of the economic analyses presented on the cost-effectiveness plane for: (A) the base case PSAs, (B)
the results of the scenario analyses and (C) the results of the prespecified subgroup analyses. DCCT, Diabetes Control and
Complications Trial; DKA, diabetic ketoacidosis; ICER, incremental cost-effectiveness ratio; MDI, multiple daily injection; PSA,
probabilistic sensitivity analysis; QALYs, quality-adjusted life years.

12 Pollard DJ, et al. BMJ Open 2018;8:e016766. doi:10.1136/bmjopen-2017-016766

 Open Access

ITT analysis where switchers are included in their origi-

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Table 5  The incremental cost-effectiveness ratio associated with insulin pumps for different HbA1c reductions (for all adults with type 1 diabetes mellitus) and annualised

10.9 mmol/mol 12.0 mmol/mol 13.1 mmol/mol

nally randomised arms, smaller HbA1c reductions than

Red, the incremental cost-effectiveness ratio is above £30,000 per quality adjusted life year gained; Orange, the incremental cost-effectiveness ratio is between £30 000 and £20
Dominates
Dominates
the ones in this analysis would likely lead to the same

£17 610
£15 515
£13 419
£11 323
ICERs. Finally, as no one study could provide sufficient
(1.2%)

£9227
£7131
£5036
£2940
£844
information on the disutility decrements associated with
diabetic events for people with type 1 diabetes, the data
come from disparate sources. This means that the magni-
tude of some events appears to be small compared with

Dominates
Dominates
others. For example, end-stage renal disease has a utility
£18 953
£16 730
£14 507
£12 284
£10 060
(1.1%)

£7837
£5614
£3391
£1167
decrement of −0.078, whereas heart failure has a higher
decrement of −0.101.
A 2015 systematic review on the cost-effectiveness of

000 per quality adjusted life year gained; Green, the incremental cost-effectiveness ratio is less than £20 000 per quality adjusted life year gained.
insulin in various countries identified four studies from
the UK, three of which presented an ICER.34 The base case
£26 258
£23 736
£21 213
£18 691
£16 169
£13 646
£11 124

ICERs in these three studies were £11 461, £25 648 and

(1.0%)

£8602
£6079
£3557
£1035
£37 712, which indicate that in two out of the three studies
that pumps had an ICER within/below the threshold range
usually used by NICE to determine the cost-effectiveness
3.3 mmol/mol 4.4 mmol/mol 5.5 mmol/mol 6.6 mmol/mol 7.7 mmol/mol 8.7 mmol/mol 9.8 mmol/mol

of technologies in the UK. However, most of the previous

cost-effectiveness analyses used a reduction in Hba1c of
£25 979
£23 494
£21 009
£18 524
£16 039
£13 554
£11 070
(0.9%)

£8585
£6100
£3615
£1130

10–13  mmol/mol (0.95%–1.2%) associated with pumps

compared with MDI, based on the meta-analysis by Weiss-
berg-Benchell et al35, which included a mixture of RCTs
and observational studies. This effect size is much larger
Dominates

than that observed in the REPOSE trial. Some of the effect

£27 951
£25 128
£22 306
£19 483
£16 661
£13 838
£11 016
(0.8%)

£8193
£5370
£2548

size in the meta-analysis may be related to the education

offered to people in the pump arms, which was not offered
to people in the MDI arms and that MDI was not admin-
istered using both long-acting and short-acting analogue
insulins in most studies included in the meta analysis. To
£34 280
£31 132
£27 985
£24 837
£21 689
£18 542
£15 394
£12 246
(0.7%)

£9099
£5951
£2803

our knowledge, REPOSE is the first large trial in adults with

type one diabetes that provides evidence on pumps versus
MDI (in which both long-acting and short-acting analogue
insulins are used) that provides equivalent diabetes educa-
tion to both trial arms. As such, this economic analysis is the
£47 667
£43 527
£39 387
£35 247
£31 107
£26 967
£22 827
£18 687
£14 547
£10 407
(0.6%)

first cost-effectiveness analysis relevant to assessing whether

£6267

pumps should be offered at the point when adults with

T1DM in the UK are eligible to receive structured educa-
tion and do not have an immediate clinical need to receive
a pump.
prices of insulin pumps and insulin pump consumables

£64 493
£58 901
£53 309
£47 717
£42 125
£36 533
£30 941
£25 349
£19 757
£14 164
(0.5%)

The key implication of this paper is that unless there is

£8572

an immediate clinical need for using a pump, clinicians in

the NHS should offer adults with T1DM a structured educa-
tion course of proven benefit, prior to considering pump
therapy. This is because when pumps+DAFNE is compared
£85 990
£79 106
£72 222
£65 338
£58 454
£51 570
£44 686
£37 802
£30 917
£24 033
£17 149

with MDI+DAFNE, the incremental health benefits are rela-

(0.4%)

tively small and the incremental lifetime costs are relatively

high. This indicates that it would not be cost-effective to
allow all adults with T1DM who are eligible for structured
education, and have no clinical need for a pump, to also
£2060 (100%) £75 710
£69 830
£63 950
£58 070
£52 189
£46 309
£40 429
£34 549
£28 668
£22 788
£16 908

immediately receive an insulin pump.

(0.3%)

A question not addressed by the REPOSE trial is

whether pumps would be clinically effective and cost-ef-
fective in patients offered the technology at some point
£1957 (95%)
£1854 (90%)
£1751 (85%)
£1648 (80%)
£1545 (75%)
£1442 (70%)
£1339 (65%)
£1236 (60%)
£1133 (55%)
£1030 (50%)

after having attended a structured education course.

Generating this evidence would require a clinical study,
which recruited participants who had previously received
a structured education course of proven benefit and

Pollard DJ, et al. BMJ Open 2018;8:e016766. doi:10.1136/bmjopen-2017-016766 13

 Open Access
randomising them to either continued MDI or pumps.
While the current literature does provide some indica-
tion of which individuals may benefit from pumps, the
clinical evidence informing these studies was not limited
to those individuals who had first received structured
education. This is important because the effectiveness of
insulin pumps would be expected to differ in this group,
with this being related to observed and unobserved
patient characteristics. One particular hypothesis that
we believe is worthwhile investigating is whether pumps
should be used in the UK by those adults with T1DM
who actively self-manage after attending a structured
education course, but either have not achieved the NICE
target HbA1c levels of less than or equal to 48 mmol/mol
(6.5%) or who have problematic hypoglycaemia. Another
important research question concerns the effectiveness
and cost-effectiveness of support programmes posteduca-
tion, so that more adults with T1DM achieve glycaemic
targets. The DAFNEplus NIHR programme grant, which
will report in 2022, is developing and testing an adapted
DAFNE course (based on previous research, behaviour
change theory and technological support) and subse-
quent structured support to improve self-management
and glucose control.36
In conclusion, the results indicate that it would not be
cost-effective to offer pumps to all adults with T1DM in the
UK, who are currently eligible to receive a structured educa-
tion course and do not have an immediate clinical need
for a pump in the UK. Use of MDI+DAFNE is estimated to
represent a better use of NHS resources than immediate
commencement on a pump. Further research is required
to improve the glycaemic control of adults with T1DM in
the UK.
Author affiliations
1 Medtronic UK Ltd.
School of Health and Related Research (ScHARR), University of Sheffield, Sheffield,
UK
2
Population Evidence and Technologies, Warwick Medical School, University of
Warwick, Coventry, UK
3
Academic Unit of Diabetes, Endocrinology and Metabolism, Department of
Oncology and Metabolism, School of Medicine and Biomedical Sciences, University
of Sheffield, Sheffield, UK
4 unrelated to REPOSE.
Clinical Trials Research Unit, School of Health and Related Research (ScHARR),
University of Sheffield, Sheffield, UK
5
RTI Health Solutions, Manchester, UK
Acknowledgements  We would like to thank Richard Jacques and Mónica
Hernández Alava for their advice on how to conduct the statistical analysis on
HbA1c and Peter Mansell for providing helpful comments on the full report.
Collaborators  Simon Heller was the chief investigator. Norman Waugh was
the deputy chief investigator. Stephanie Amiel, Mark Evans, Fiona Green, Peter
Hammond, Alan Jaap, Brian Kennon, Robert Lindsay and Peter Mansell were site
principal investigators and contributed to the study design and data interpretation.
Jane Baillie, Anita Beckwith, Helen Brown, Karen Callaby, Katy Davenport, Sarah
Donald, Jackie Elliott, Leila Faghahati, Sara Hartnell, Allison Housden, Kalbir Kaur
Pabla, Nicola Croxon, Sheena Macdonald, Muna Mohammed, Vicky Steel, Katy
Valentine, Pamela Young, Ann Boal, Patsy Clerkin, Lynn Doran, Joanne Flynn, Emma
Gibb, Hilary Peddie, Bernie Quinn, Helen Rogers, Janice Shephard, Janet Carling,
Ann Collins, Laura Dinning, Christine Hare, Joyce Lodge, Sutapa Ray, Debora Brown,
Jenny Farmer, Alison Cox, Chris Cheyette, Pratik Choudhary, Linda East, June Ellul,
Katherine Hunt, Kimberley Shaw, Ben Stothard, Lucy Diamond, Lindsay Aniello,
Debbie Anderson, Kathy Cockerell, Vida Heaney, Alison Hutchison, Nicola Zammitt,
14
Gayna Babington, Gail Bird, Janet Evans, Tasso Gazis, Nicola Maude, Karen Nunnick,
BMJ Open: first published as 10.1136/bmjopen-2017-016766 on 7 April 2018. Downloaded from http://bmjopen.bmj.com/ on 28 August 2018 by guest. Protected by copyright.
Dawn Spick, Laura Fenn, Carla Gianfrancesco, Valerie Gordon, Linda Greaves, Susan
Hudson, Valerie Naylor, Chloe Nisbet, Carolin Taylor, Karen Towse and Candice
Ward contributed at sites to participant recruitment, intervention delivery and data
collection. Cindy Cooper, Gemma Hackney, Diana Papaioannou, Emma Whatley
and David White provided central trial management, oversight and monitoring.
Mike Bradburn, Michael Campbell, Munya Dimairo and Ellen Lee contributed to the
statistics. Hasan Basarir, Alan Brennan, Simon Dixon and Daniel Pollard contributed
to the health economics. Nina Hallowell, Jackie Kirkham, Julia Lawton and David
Rankin designed and undertook the qualitative work. Katharine Barnard led the
quantitative psychosocial work. Timothy Chater and Kirsty Pemberton provided data
management. Fiona Allsop and Lucy Carr provided central administration. Pamela
Royle conducted literature searches and exploratory analyses. Gill Thompson
and Sharon Walker provided central DAFNE support. Pauline Cowling conducted
the fidelity assessment. Henry Smithson provided user representation on the
management group.
Contributors  DJP contributed to the design of all of the health economic analyses
and conducted all statistical and modelling analyses used in this paper. AB oversaw
the design and implementation of the modelling analyses. SD, oversaw the design
and implementation of the economic analysis of the trial data and contributed to
the estimation of the treatment costs used in the long-term economic analyses.
AB, SD, NW, JE, SH and MC contributed to the design of the trial. NW, JE and SH
provided clinical input into the design of the economic analyses. MC designed the
statistical analysis plan. EL implemented the statistical analysis plan, parts of which
were used in the economic evaluation. HB and DW contributed to data collection
for the economic analyses. AB and HB designed and developed previous versions
of the economic model used in these analyses. DJP wrote the first draft. All authors
approved the final draft. DJP is the guarantor.
Funding  This research was funded by the UK Health Technology Assessment
Programme (project number 08/107/01). The research was sponsored by Sheffield
Teaching Hospitals NHS Foundation Trust. The clinical sites taking part were:
Cambridge University Hospitals NHS Foundation Trust, Dumfries and Galloway
Royal Infirmary, NHS Greater Glasgow and Clyde, Harrogate and District NHS
Foundation Trust, King’s College Hospital NHS Foundation Trust, NHS Lothian,
Nottingham University Hospitals NHS Trust and Sheffield Teaching Hospitals NHS
Foundation Trust. We also acknowledge the financial support of the Research
and Development Programmes of the Department of Health for England and
the Scottish Health and Social Care Directorates, which supported the costs of
consumables and of Medtronic UK Ltd, which provided the insulin pumps for the
trial.
Disclaimer  The views and opinions expressed herein are those of the authors and
do not necessarily reflect those of the HTA, NIHR, NHS, the Department of Health or
Competing interests  SH reports personal fees from Sanofi Aventis and personal
fees and other from NovoNordisk and Eli Lilly, outside the submitted work. JE
reports personal fees from Astra Zeneca, Merck Sharpe Dohme and Takeda,
personal fees and non-financial support from Eli Lilly, Novonordisk and Sanofi,
outside the submitted work. NW reports receiving two days of consultancy fees
from Novo Nordisk on topics including alternatives to network meta-analysis,
Patient consent  Obtained.
Ethics approval  Research Ethics Committee (REC) North West, Liverpool East.
Provenance and peer review  Not commissioned; externally peer reviewed.
Data sharing statement  Requests for patient level data and statistical code
should be made to the corresponding author and will be considered by the REPOSE
trial management group who, although specific consent for data sharing was not
obtained, will release data on a case-by-case basis following the principles for
sharing patient level data as described by Smith et al (2015). The presented data do
not contain any direct identifiers; we will minimise indirect identifiers and remove
free-text data to minimise the risk of identification.
Open Access This is an Open Access article distributed in accordance with the
terms of the Creative Commons Attribution (CC BY 4.0) license, which permits
others to distribute, remix, adapt and build upon this work, for commercial use,
provided the original work is properly cited. See: http://​creativecommons.​org/​
licenses/​by/​4.​0/
© Article author(s) (or their employer(s) unless otherwise stated in the text of the
article) 2018. All rights reserved. No commercial use is permitted unless otherwise
expressly granted.
Pollard DJ, et al. BMJ Open 2018;8:e016766. doi:10.1136/bmjopen-2017-016766

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